Effects of diazepam and picrotoxin on hyponeophagia in rats.

The effects of diazepam (1 mg/kg), picrotoxin (1.5 mg/kg) and both treatments on hyponeophagia in male and female rats were studied. Diazepam reduced eating latency and enhanced the total amount eaten in the test. Picrotoxin increased approach and eating latencies and reduced amount eaten, females being more sensitive to these actions. Behavioural sensitivity to diazepam was reduced by picrotoxin for approach latency but enhanced for eating latency. These findings are discussed in connection with the GABA hypothesis of the actions of benzodiazepines.

Effects of diazepam and of serotonin agonists on hyponeophagia in rats.

The effects of serotonin agonists, fenfluramine (2 mg/kg) and 5-methoxy N,N dimethyltryptamine (5-MeODMT, 2.5 mg/kg) on hyponeophagia were studied both alone and in combination with diazepam (1 mg/kg). Male and female rats were used but sex differences were not found. The serotonin agonists enhanced hyponeophagia while diazepam attenuated it and antagonised the actions of both serotonin agonists. These findings are discussed in connection with the serotonin hypothesis of benzodiazepine action with the conclusion that diazepam acts distally to serotonergic drugs on hyponeophagia.

The effects of parachlorophenylalanine and stimulus intensity on open-field test measures in rats.

An inhibitor of 5-hydroxytryptamine synthesis, p-chlorophenylalanine (PCPA), or an inert saline solution was administered intraperitoneally to rats. At maximum depletion of serotonin (72 hr after injection), the rats were tested in the standard, four-day open-field test. A further four days of testing in the open field in which the sound level was raised from the standard 78 to 93 dB showed that, while PCPA increased defaecation in both sexes and under both sound levels, the controls increased defaecation at the higher level stimulus intensity, whereas PCPA-injected rats defaecated less. Parachlorophenylalanine increased ambulation in males on the first day of open-field testing but not in females. On the remaining seven days of testing PCPA markedly reduced ambulation in females but did not affect ambulation in males. Across-trial habituation of neither the defaecation nor the ambulation measure was influenced by PCPA.

Drug interactions do not support reduction in serotonin turnover as the mechanism of action of benzodiazepines.

Interactions between 5-methoxy, N,N-dimethyltryptamine (5-MeODMT), chlordiazepoxide and para-chlorophenylalanine (pCPA) on conflict behaviour were studied. 5-Methoxy, N,N-dimethyltryptamine (1.0 and 3.0 mg/kg), induced observable effects and reduced unpunished response rates but did not affect punished behaviour either alone, on in the presence of 5 or 10 mg/kg chlordiazepoxide. However, 5-MeODMT (1 mg/kg) reversed the anti-conflict effects of chronic administration of pCPA (100 mg/kg). Chronic administration of pCPA did not prevent the increase in punished response rates induced by chlordiazepoxide (5 mg/kg). These findings are discussed in the context of the serotonin hypothesis of benzodiazepine action, with the conclusion that benzodiazepines act at a site distal to that of serotonergic drugs on conflict behaviour.

Hyponeophagia and arousal in rats: effects of diazepam, 5-methoxy-N,N-dimethyltryptamine, d-amphetamine and food deprivation.

A modified hyponeophagia test is described as an animal model of anxiety. The effects of 0, 0.3, 1.0, 3.0 and 10 mg/kg diazepam, given both acutely and for 7 days pretest, were assessed in rats. Acutely, diazepam reduced hyponeophagia over the dose range 0.3-3.0 mg/kg but 10.0 mg/kg produced sedation and large variability. Chronically, the dose-response relationships were monotonic and the maximal effect was increased, suggesting that differential tolerance occurs to the sedative, but not to the anxiolytic, effects of this drug. Increased food deprivation did not mimic benzodiazepine effects on hyponeophagia, and actually prolonged eating latency in rats treated with 5-methoxy-N,N-dimethyltryptamine (2.5 mg/kg), which does not support an interpretation of diazepam effects in terms of appetitive actions. An arousal hypothesis of hyponeophagia was proposed and supported by the antagonism of the sedative effects of 10.0 mg/kg diazepam by d-amphetamine (0.5 mg/kg). Although both male and female rats were used throughout, sex differences were few in these studies.

Hyponeophagia in the Roman rat strains: effects of 5-methoxy-N,N-dimethyltryptamine, diazepam, methysergide and the stereoisomers of propranolol.

The effects of 5-MeODMT (2.5 mg/kg), diazepam (1 mg/kg), methysergide and the stereoisomers of propranolol (6 mg/kg) on hyponeophagia were studied in both sexes of the Roman strains of rats, selectively bred for acquisition of a two-way conditioned avoidance response. Diazepam, methysergide and 1-propranolol increased feeding in a novel environment whilst 5-MeODMT decreased it and d-propranolol was inactive. Several strain differences in drug responsiveness occurred, the Roman Low Avoidance subjects being most sensitive to all drugs tested as well as being most neophobic. A sex difference in 5-MeODMT sensitivity was also found, female rats of the Roman High and Control Avoidance strains being more sensitive than males. The findings are discussed in connection with differences in arousal and biochemical parameters between these strains.

Sex and strain differences in benzodiazepine receptor binding in Roman rat strains.

Specific [3H]flunitrazepam binding was determined for five brain regions in both sexes of the three Roman rat strains. Small strain differences and a large Sex-Region interaction were detected, benzodiazepine receptor binding being significantly higher in females in the two cortical areas and the cerebellum, but significantly lower in the striatum and hippocampus. These findings are discussed in the context of sex and strain differences in behavior and benzodiazepine sensitivity.

Beta-adrenoceptor antagonists may attenuate hyponeophagia in the rat through a serotonergic mechanism.

The unconditioned inhibition of feeding in a novel setting (hyponeophagia) was reduced by propranolol and another potentially centrally acting beta-adrenoceptor antagonist, pindolol but not by a peripherally acting one, atenolol. A similar attenuation of hyponeophagia was seen following the 5-HT antagonist methysergide but no consistent effects were observed following some dopamine antagonist drugs. 5-Methoxy N,N-dimethyltryptamine (5-MeODMT), a compound with central 5-HT agonist properties, consistently potentiated hyponeophagia, an effect which was reversed by the centrally acting beta-adrenoceptor antagonists and by methysergide. The results are interpreted as evidence for a 5-HT mediation of hyponeophagia and for a probable central 5-HT antagonist role for propranolol and pindolol.

Relationships between hyponeophagia, diazepam sensitivity and benzodiazepine receptor binding in eighteen rat genotypes.

Rats of 18 genotypes derived from the selected Roman strains were tested for hyponeophagia in a control condition and following diazepam (1 mg/kg). Subsequently, benzodiazepine receptor binding was measured in the cortical/striatal region. Hyponeophagia in the control condition correlated strongly with diazepam sensitivity, but benzodiazepine receptor titres did not correlate significantly with either control behavior or drug responsivity. These findings are discussed in the contexts of the arousal hypothesis of hyponeophagia and of postulated relationships between benzodiazepine receptors and emotionality.

Alcohol selection by strains of rats selectively bred for behavior.

Maudsley, Roman and Tryon rats showed strain differences in alcohol intake and alcohol preference ratio, and sex differences in alcohol intake.

The Maudsley reactive and nonreactive strains of rats: a clarification.

The origin of the Maudsley reactive and nonreactive strains of rats and the construction of the survey of researches using them are briefly reviewed in the light of Archer's criticisms. The reasons for reasserting that they represent a valid dichotomy in emotionality are summarized.

The Maudsley reactive and nonreactive strains of rats: a survey.

Experiments with two strains of rats, the Maudsley Reactive and Nonreactive, developed in London, England, and which were performed during 1964--1974 by a variety of investigators are summarized in a table. It is concluded that the results support the strains' standing as exemplars of differences in emotional reactivity.

The effects of nicotine on two-way avoidance conditioning in bi-directionally selected strains of rats.

Rats of both sexes from the genetically selected Roman High Avoidance (RHA), the Roman Low Avoidance (RLA) and the Roman Control (RCA) strains were given one 30-min session of two-way escape-avoidance conditioning (30 trials) in a shuttle box with a buzzer as the conditioned stimulus and shock as the unconditioned stimulus in a factorial design involving three time intervals (0, 15 and 30 min) following one subcutaneous injection of saline or of nicotine in five doses (0.05, 0.1, 0.2, 0.4, or 0.8 mg/kg of body weight). Six measures relating to performance were analysed in whole or part. While the number of avoidance responses showed the expected strain differences, no effect of dose or delay interval could be detected. Avoidance and escape latencies and intertrial activity showed some effects of these variables, especially in interaction with sex and strain. Dose determined pre-sessional activity, but its effect was strain dependent. The failure to confirm previous findings is discussed in the context of other instances in the literature, and the results of an operant experiment confirming the continuing sensitivity of the Roman strains to the effects of nicotine are reported.

A simplified triple-test cross analysis of alcohol preference in the rat.

Reanalyses of first-degree biometrical genetic data from previous studies of alcohol preference in the mouse revealed little consistency beyond a basic additive genetic component. A simplified triple-test cross in the rat investigated the genetic architecture of alcohol preference for a 10% (w/v) alcohol solution or water. An initial survey of eight selected and inbred strains identified high- and low-scoring strains, the MNR and the ACI respectively, which were crossed as tester lines to six strains ( the RHA, RLA, TMB, TMD, MNR, and ACI) to produce the required set of largely F1 families. The additive-dominance model proved adequate for males, and directional dominance for low alcohol preference was found on all three measures: alcohol intake, alcohol preference ratio, and alcohol calorie contribution ratio. For females the model was adequate only for alcohol preference ratio, which showed ambidirectional dominance. The relevance of such genetic architecture to an animal model of alcoholism and to the evolution of alcohol drinking in the rat is discussed.

A factor analysis of body build in the rat.

Following a survey of the problems associated with the comparative study of measures of physique in domesticated and laboratory animals, techniques were developed for the measurement of body build in the adult albino laboratory rat (Rattus norvegicus). They involved anesthetisation of the animals and the use of calipers and a simple apparatus devised for the purpose. The 17 measures taken on 100 rats, 50 of each sex, are detailed and the reasons for excluding other given. Intercorrelations of all the measures and their reliability co-efficients, which were judged satisfactory, are presented. The tables of intercorrelations, one for each sex, were factor analysed separately, and rotations to simple structure performed. Two factors were identified, one having factor saturations on measures of body length and the other similarily defining body width. This pattern was similar for the two sexes and a single index of body build was therefore proposed in which the length of the rear foot is divided by the width of the shoulder girdle and multiplied by 100 to avoid decimals. The use of the index in other investigations is mentioned.

Single alternation with water reward:effects of sodium amobarbital on two strains of rats selectively bred for high and low emotionality.

The action of sodium amobarbital is studied during the patterning effect in rats selectively bred for low and high emotionality. The drug disrupts patterned running in the goal section of the alley in Maudsley non-reactive but not in Maudsley reactive rats for the last five trial-pairs. Sodium amobarbital also affects the behavior of these strains in a differential manner, in start and run sections, during the first trial-pair. The results show that a function-related physiological change has taken place in the Maudsley strains of rats.

Analysis of two-way escape-avoidance conditioning measures from a diallel cross of eight strains of rats.

In a study designed to investigate genotype-environment interaction, eight strains of laboratory rats were crossbred in a replicated diallel cross employing infantile stimulation and its absence as environmental treatments. This paper reports on measures of the acquisition of two-way escape-avoidance conditioning, comprising number of avoidances, avoidance and escape latencies, and intertrial and presessional crossings, which were subjected to biometrical genetical analysis, all but the last successfully. Additive variation was prominent throughout and some measures showed directional dominance. Effects of stimulation were seen in avoidance number and crossings. The analysis of avoidances by successive blocks of trials using covariance:variance graphs revealed differences in the way the strains varied with respect to the changing relationships of proportions of dominant and recessive alleles governing this behavior. The results are discussed in the light of previous data and of their evolutionary implications.